Mike Cahill

BSc (Hons 1) in Zoology & Biochemistry, School of Biological Sciences, Faculty of Science, UNSW, Sydney, 1988. Ph.D. in Molecular Cell Biology, School of Pathology, Faculty of Medicine, University of New South Wales, Sydney. 1996.

Dr Cahill completed a BSc (hons I) in Zoology and Biochemistry from the School of Biological Sciences at the University of NSW, Sydney, and subsequently obtained his PhD in Molecular Cell Biology (on proto-oncogene c-fos gene regulation and signal transduction) as an external student of the Department of Pathology, School of Medicine of the University of NSW. The laboratory work for his doctoral degree was performed in the group of Prof. Alfred Nordheim, who was then at the Institute of Molecular Biology at the Medizinische Hochschule Hannover, in Germany. After doing his PhD and follow-up postdoc work in Hannover he spent one year as a postdoctoral Scientist working on Fos-family gene regulation at The John Curtin School of Medical Research at the Australian National University in Canberra, where he was introduced through a guest lecture by Professor Keith Williams to the then emerging field of Proteomics. Working in the field of signal transduction, he was then trying to identify kinases that anonymously phosphorylated my target proteins, only to frustratingly vanish unidentified back into the cloaking shadows of the unchartered cytoplasm from whence they had appeared. This field of proteomics offered new strategies to tackle the biology cell signalling, and indeed the broad panorama of cell biology.

These were exciting developments, and he decided immediately that he wanted to work in proteomics because it showed the potential to eventually address just the questions that he was trying to ask in his own research. At that stage (in 1996) the Australian Proteome Analysis Facility (APAF) had just been established, and he assessed that there was no chance of him securing funds in Australia to work on proteomics. Therefore he moved back to Germany where his Ex-PhD supervisor, Alfred Nordheim, had just accepted a Professorship at the Department of Molecular Biology, in the Interfaculty Institute of Cell Biology at the University of Tuebingen, and he offered Dr Cahill the opportunity to initiate proteomics activities in his brand new and empty institute. Those activities were the direct genetic ancestor of the modern Proteomics Centre at Tuebingen, which was founded in 2003.

However before that centre was officially opened he had left academia. Realising that proteomics techniques detected only a fraction of all cellular proteins, he was working on strategies to improve protein detection: involving a vision of large two-dimensional protein separation gels combined with sensitive multiplexed radioactive protein detection. This led to his co-foundation of a proteomics-based biotechnology company in February 2000. One year later that company underwent a corporate merger to form ProteoSys AG, based in Mainz Germany, where he initially served on the managerial board and as Chief Research Officer and co-founding scientist until he left to return to Australia in 2007. At ProteoSys, with the support of a talented team of colleagues, they were able to develop the technological proteomics platform envisioned in the business plan and to experimentally focus those newly acquired tools onto several cancer systems. Those methods in turn revealed exciting cell biology, which closed the circle on his professional interests of oncogenic signal transduction.

In 2008 Dr Cahill 'moved back home' by re-entering academic life in Australia as a biochemistry lecturer at Charles Sturt University in Wagga Wagga, where the climate and landscape are similar to Wellington NSW, where he grew up. And here he is.

In June 2010 the People's Daily newspaper, the most influential in China, featured his work in an article on international collaborative research at Charles Sturt University. (Original article in Chinese; Google translation into English). See his publications in collaboration with Chinese colleagues.

On 11 July 2014 Dr Cahill featured in a Prime7 News TV item about cancer research at Charles Sturt University in Wagga.

Since August 2013 Dr Cahill has been a scientific advisor for Cognition Therapeutics Inc (Pittsburgh; www.cogrx.com),* whose small molecule pharmaceuticals that target PGRMC1 reverse symptoms of Alzheimer's Disease in mice, such as reducing plaque density and improving memory functions. Read more about PGRMC1 research under the Research and Publication headings. Because cancer and Alzheimer's disease are extremely relevant to the ageing communities of CSU's geographical footprint, Dr Cahill's molecular cell research aligns excellently with CSU's strategic research aims to benefit its communities.

* For legal reasons: Any advice provided to Cognition Therapeutics by Dr Cahill is explicitly his own opinion, and does not represent the views of Charles Sturt University or its management.

Teaching

Teaching philosophy

Dr Cahill teaches using a blended learning approach where students have access to multiple media and avenues to achieve their learning objectives. These range from face to face lectures, podcasting, linking to online e-resources, lab practicals, problem based learning modules, and one-on-one mentoring, as well as answering student queries by email, telephone, BLOG thread, or chat. My door is always open to students, but they are advised to make an appointment if they want to be certain that I am available.

Research Profiles

The role of PGRMC1 in cancer and metabolic regulation

At ProteoSys AG, a proteomics-centred company which I co-founded, I headed cancer research. After that indication area was discontinued due to insufficient funds I could choose any result in the then current cancer portfolio to pursue in an academic career. By far the most promising protein in the cancer portfolio of ProteoSys, the veritable jewel in the crown, was the protein Progesterone Receptor Membrane Component 1 (PGRMC1), which we had detected to be differentially phosphorylated between breast cancers differing in expression levels of the estrogen receptor. Whereas these results had been submitted for patent applications between 2004-2007 (WO2006029836; WO2007039189; WO2008037449), a chronic internal funding shortage for the project within the company had prevented the level of biological characterisation that will be necessary to elucidate the precise role of PGRMC1 in cancer. That elucidation represents my current research priority. Although it is a small protein, PGRMC1 has been implicated in a wide variety of biological functions (See Cahill 2007). In fact it is highly likely that PGRMC1 is involved at a crucial nexus position in a convergent inter-regulated yet hitherto undescribed signalling system (which includes the regulation of steroid synthesis) whose activity determines the survival prognosis of cancer cells (Neubauer et al., 2008). PGRMC1 also regulates the steroid-mediated onset of vasculogenesis that is so crucially important in metastatic biology (Neubauer et al., 2009), and is induced at the time and place in cancers where it regulate the onset of oxygen-independent tumour-specific energy metabolism (Figure 1)

Figure 1.The induction of PGRMC1 (red) in the hypoxic zone (redox stress) surrounding the necrotic core (central dark green staining) of a ductal carcinoma in situ from a breast cancer patient tissue section. The estrogen receptor (outer green staining) stains in a halo surrounding the hypoxic zone but is downregulated where PGRMC1 is upregulated; From Neubauer et al., (2008). In the same paper we showed that PGRMC1 phosphorylation differed between breast cancers, and that phosphorylation site mutants protected cancer cells from redox induced death.

Since August 2013 I have been a scientific advisor for for Cognition Therapeutics Inc (Pittsburgh; www.cogrx.com),* who have developed anti-Alzheimer drugs which target PGRMC1 leading to reversal of the symptoms of Alzheimer's Disease in mice. This work was published in November 2014 by Izzo et al. (http://dx.doi.org/10.1371/journal.pone.0111899).

Projects available on PGRMC1

There are several potential research projects available to study the role of this exciting protein in cancer and cell metabolism. Methods involve cell imaging, cloning, mutagenesis, cell culture, and general cell molecular biological techniques. Students interested in pursuing Honours or Doctoral studies in a stimulating scientific environment working on the mechanistic molecular cell biology of cancer or pharmacology are encouraged to contact me. The commitment to either undergraduate or postgraduate study is a vitally important step that hones the future career path of any student. The PGRMC1 signalling project offers a scientific environment and a compellingly urgent research topic that will enable students who are willing to apply themselves to reach their scientific potential at this crucial stage of their careers. The School of Biomedical Sciences is also a great place to work, and we have a lot of fun here too!

Human Ageing

The earliest stories passed down to us in myths and sagas contain reference to secret and powerful treatments that could prolong the ageing process in those that took them, or to extremely long lived gods or royal characters. These include the Indo-European gods (e.g., the apples of the Hesperides and Ambrosia in Greek, the apples of Idun and Mead for the Germanic Aesir, Homa and Soma for the early Indo-Iranians), Manetho's long lived early predynastic Egyptian kings, the Epic of Gilgamesh (the earliest attested literature, where the survivor of Noah's flood had the secret of immortality), and the related flood account in Genesis, where Noah's immediate male ancestors all lived many hundreds of years, including Methuselah, the oldest of them all ("But what good is livin', when no girl will give-in to a man who is 900 years"). Clearly, this theme has long aroused the excitement of many story tellers.

Since the late 1990's I have been interested in ancient myths and stories concerning long-lived individuals from bygone days. In my book - Paradise Rediscovered (2012, Glass House Books, Brisbane). I argue that many of these old tales contain some historically accurate information that permits us to attempt reconstruction of a social system that existed perhaps more than 8000 years ago. This includes the location of a religious centre that was flooded by rising sea levels at the mouth of the modern Black Sea after a monumental clash of two cultures, as described by Plato's Critias and Timaeus, The Book of Enoch, and the Epic of Gilgamesh, and indeed in residual form is reflected in biblical Genesis. You can see my poster on this topic (TEXTUAL SUPPORT FOR A 6400 BC BLACK SEA FLOOD) as presented at the ATLANTIS 2011 conference (25-27 June 2011, Santorini, Greece). Two chapters by me in the conference proceedings discuss the hypothesis. Most of those ancient tales also contain as a recurrent element of precisely the same theme of human longevity referred to above, which caused me to wonder whether some elite section of humanity (i.e. 'the gods') in preantiquity might have commanded a real elixir to extend lifespan, as reconstructed from those same reliable sources, whose recipe has long since been lost and which lingers only as legend in our collective consciousness. Paradise Rediscovered explores that hypothesis.

Recent findings in cell and organism biology have made this idea particularly piquant. Over the past two decades ageing studies in model organisms have revealed evolutionarily conserved pathways that affect the rate of ageing in organisms from yeast, roundworms, and fruit flies to mice (Guarente & Kenyon, 2000; Kenyon, 2010; Kenyon 2011), leading to speculation that ageing may be a treatable phenomenon in the future (Hadley et al., 2005). One such pathway involves the mTOR (mammalian Target Of Rapamycin) signalling pathway. Experimental developments in model organisms over the last 20 years have led to the recent demonstration that inhibiting mTOR in mice with the dug rapamycin indeed increases the life-span of those mice (Harrison et al., 2009). Although the effect was relatively modest, and the ages of the longest lived mice in the rapamycin treatment were no longer than the controls, this represented a veritable landmark result. Rapamycin is an immune immunosuppressant that destroyed the immune systems of those mice, but the result demonstrated preliminary proof of concept and proof of mechanism that ageing might be pharmacologically addressed in mammals (and hence in humans). These are the two major acceptance criteria for the pharmaceutical industry to accept a project into their high throughput screening pipelines. It is quite feasible (but don't hold your breath) that in the foreseeable future humans may age more slowly, so that a 60 year old (or 180 year old) person may retain the body of a modern 25 year old by growing old more slowly. The advent of antibiotics after WWII heralded a medical revolution of similar importance, and such a breakthrough in ageing research is quite within the realms of possibility in the coming years. Using results from comparative mythology, comparative ethnography, and archaeology, it may just be possible reconstitute the ingredients of a putative ancient elixir, as described in - Paradise Rediscovered. This represents an ongoing research interest of mine.

Invited Presentations

John Curtin School of Medical Research School Seminar Series, Australian National University. 31st July, 2009. Towards the role(s) of the putative membrane steroid receptor PGRMC1 in breast cancer. M. Cahill.